dsRNA-induced immunity targets plasmodesmata and is suppressed by viral movement proteins.

Emerging evidence indicates that in addition to its well-recognized functions in antiviral RNA silencing, dsRNA elicits pattern-triggered immunity (PTI), likely contributing to plant resistance against virus infections. However, compared to bacterial and fungal elicitor-mediated PTI, the mode-of-action and signaling pathway of dsRNA-induced defense remain poorly characterized. Here, using multicolor in vivo imaging, analysis of GFP mobility, callose staining, and plasmodesmal marker lines in Arabidopsis thaliana and Nicotiana benthamiana, we show that dsRNA-induced PTI restricts the progression of virus infection by triggering callose deposition at plasmodesmata, thereby likely limiting the macromolecular transport through these cell-to-cell communication channels. The plasma membrane-resident SOMATIC EMBRYOGENESIS RECEPTOR-LIKE KINASE 1, the BOTRYTIS INDUCED KINASE1/AVRPPHB SUSCEPTIBLE1-LIKE KINASE1 kinase module, PLASMODESMATA-LOCATED PROTEINs 1/2/3, as well as CALMODULIN-LIKE 41 and Ca2+ signals are involved in the dsRNA-induced signaling leading to callose deposition at plasmodesmata and antiviral defense. Unlike the classical bacterial elicitor flagellin, dsRNA does not trigger a detectable reactive oxygen species (ROS) burst, substantiating the idea that different microbial patterns trigger partially shared immune signaling frameworks with distinct features. Likely as a counter strategy, viral movement proteins from different viruses suppress the dsRNA-induced host response leading to callose deposition to achieve infection. Thus, our data support a model in which plant immune signaling constrains virus movement by inducing callose deposition at plasmodesmata and reveals how viruses counteract this layer of immunity.

Self-templating assembly of soft microparticles into complex tessellations.

Encoding Archimedean and non-regular tessellations in self-assembled colloidal crystals promises unprecedented structure-dependent properties for applications ranging from low-friction coatings to optoelectronic metamaterials1-7. Yet, despite numerous computational studies predicting exotic structures even from simple interparticle interactions8-12, the realization of complex non-hexagonal crystals remains experimentally challenging13-18. Here we show that two hexagonally packed monolayers of identical spherical soft microparticles adsorbed at a liquid-liquid interface can assemble into a vast array of two-dimensional micropatterns, provided that they are immobilized onto a solid substrate one after the other. The first monolayer retains its lowest-energy hexagonal structure and acts as a template onto which the particles of the second monolayer are forced to rearrange. The frustration between the two lattices elicits symmetries that would not otherwise emerge if all the particles were assembled in a single step. Simply by varying the packing fraction of the two monolayers, we obtain not only low-coordinated structures such as rectangular and honeycomb lattices, but also rhomboidal, hexagonal and herringbone superlattices encoding non-regular tessellations. This is achieved without directional bonding, and the structures formed are equilibrium structures: molecular dynamics simulations show that these structures are thermodynamically stable and develop from short-range repulsive interactions, making them easy to predict, and thus suggesting avenues towards the rational design of complex micropatterns.

Visible-Light-Driven Photocatalytic H2 Production Using Composites of Co-Al Layered Double Hydroxides and Graphene Derivatives.

The direct conversion of solar energy into chemical energy represents an enormous challenge for current science. One of the commonly proposed photocatalytic systems is composed of a photosensitizer (PS) and a catalyst, together with a sacrificial electron donor (ED) when only the reduction of protons to H2 is addressed. Layered double hydroxides (LDH) have emerged as effective catalysts. Herein, two Co-Al LDH and their composites with graphene oxide (GO) or graphene quantum dots (GQD) have been prepared by coprecipitation and urea hydrolysis, which determined their structure and so their catalytic performance, giving H2 productions between 1409 and 8643 µmol g-1 using a ruthenium complex as PS and triethanolamine as ED at 450 nm. The influence of different factors, including the integration of both components, on their catalytic behavior, has been studied. The proper arrangement between the particles of both components seems to be the determining factor for achieving a synergistic interaction between LDH and GO or GQD. The novel Co-Al LDH composite with intercalated GQD achieved an outstanding catalytic efficiency (8643 µmol H2 g-1) and exhibited excellent reusability after 3 reaction cycles, thus representing an optimal integration between graphene materials and Co-Al LDH for visible light driven H2 photocatalytic production.

Discovery of selective monosaccharide receptors via dynamic combinatorial chemistry.

The molecular recognition of saccharides by synthetic hosts has become an appealing but elusive task in the last decades. Herein, we combine Dynamic Combinatorial Chemistry (DCC) for the rapid self-assembly and screening of virtual libraries of receptors, with the use of ITC and NMR to validate the hits and molecular modelling to understand the binding mechanisms. We discovered a minimalistic receptor, 1F (N-benzyl-L-phenylalanine), with considerable affinity for fructose (Ka = 1762 M-1) and remarkable selectivity (>50-fold) over other common monosaccharides. The approach accelerates the discovery process of receptors for saccharides.

Contribution of Microorganisms with the Clade II Nitrous Oxide Reductase to Suppression of Surface Emissions of Nitrous Oxide.

The sources and sinks of nitrous oxide, as control emissions to the atmosphere, are generally poorly constrained for most environmental systems. Initial depth-resolved analysis of nitrous oxide flux from observation wells and the proximal surface within a nitrate contaminated aquifer system revealed high subsurface production but little escape from the surface. To better understand the environmental controls of production and emission at this site, we used a combination of isotopic, geochemical, and molecular analyses to show that chemodenitrification and bacterial denitrification are major sources of nitrous oxide in this subsurface, where low DO, low pH, and high nitrate are correlated with significant nitrous oxide production. Depth-resolved metagenomes showed that consumption of nitrous oxide near the surface was correlated with an enrichment of Clade II nitrous oxide reducers, consistent with a growing appreciation of their importance in controlling release of nitrous oxide to the atmosphere. Our work also provides evidence for the reduction of nitrous oxide at a pH of 4, well below the generally accepted limit of pH 5.

Double myelomeningocele repair by fetal surgery with a single micro-hysterotomy.

INTRODUCTION: Open spina bifida (OSB) is the most common congenital anomaly of the central nervous system. It is associated with severe neurodevelopmental delay, motor impairment, hydrocephalus, and bowel and bladder dysfunction. In selected cases, intrauterine spina bifida repair has been shown to improve neonatal outcomes. Rarely, the spine can have a double defect compromising two different segments and there is a lack of evidence on the feasibility and benefits of intrauterine repair in these cases. CASE PRESENTATION: We present a case with both cervicothoracic and lumbosacral myelomeningocele, Arnold-Chiari malformation type II, and bilateral ventriculomegaly, that was treated successfully at 25 weeks with open micro-neurosurgery. Double myelomeningocele was successfully treated through a single 2cm micro-hysterotomy, by performing external versions to sequentially expose and repair both defects. Weekly postoperative follow-up showed no progression of ventriculomegaly or complications attributable to the procedure. Preterm rupture of membranes prompted a conventional cesarean delivery at 32 weeks of gestation. Neurodevelopmental outcome at 20 months was within normal ranges, having achieved ambulation without orthopedic support, and with no need for ventriculoperitoneal shunting. CONCLUSION: This report demonstrates for the first time the feasibility of double OSB repair through a single 2cm micro-hysterotomy, suggesting that selected isolated cases of double myelomeningocele could be candidates for fetal intervention. Further prospective studies should be carried out to assess the potential benefit of double OSB intrauterine open repair.

Downregulation of Serotonergic System Components in an Experimentally Induced Cryptorchidism in Rabbits.

Cryptorchidism (CO) or undescended testes is defined as the failure of one or both testes to be positioned inside the scrotum. Typically, cryptorchidism is detected at birth or shortly thereafter, and in humans, it is considered to be part of the testicular dysgenesis syndrome (TDS), a complex pathology regarding the male reproductive system that apparently involves the interaction of both genetic and environmental harmful factors, mainly during embryonic development. Serotonin (5-HT) is an ancient molecule that participates in a broad range of body functions, and in recent years, its importance in reproduction has started to be elucidated. In male pathologies such as infertility, varicocele, erectile dysfunction, and primary carcinoid tumors, an increase in 5-HT concentration or its metabolites in the blood, semen, and urine has been directly related; nevertheless, the role of 5-HT in CO remains unknown. In the present work, our goal was to answer two important questions: (1) whether some serotonergic system components are present in adult male Oryctolagus cuniculus (chinchilla rabbit) and (2) if there are changes in their expression in an experimental model of CO. Using histological, molecular, and biochemical approaches, we found the presence of some serotonergic system components in the adult chinchilla rabbit, and we demonstrated that its expression is downregulated after CO was pharmacologically induced. Although we did not test the role of 5-HT in the etiology of CO, our results suggest that this indoleamine could be important for the regulation of steroidogenesis and spermatogenesis processes in the chinchilla rabbit during adulthood. Finally, in parallel experimental series, we found downregulation of kynurenine concentration in COI rabbits when compared to control ones, suggesting that CO could be affecting the kynurenine pathway and probably testicular immune privilege which in turn could lead to infertility/sterility conditions in this disorder.

New hard tick (Acari: Ixodidae) reports and detection of Rickettsia in ticks from Sierra Nevada de Santa Marta, Colombia.

The Sierra Nevada de Santa Marta (SNSM), located in northern Colombia, is considered a geographical island with high levels of biodiversity and endemism. However, little is known about tick species and their associated microorganisms at the SNSM. In this study we sampled host-seeking ticks in areas of the town of Minca within the SNSM. We collected 47 ticks identified as Amblyomma pacae, Amblyomma longirostre, Amblyomma ovale, Amblyomma mixtum, Haemaphysalis juxtakochi, Ixodes sp. cf. Ixodes affinis and Ixodes sp. Of these ticks, we tested for Rickettsia spp. by amplifying the gltA, SCA1, and 16S rRNA genes via PCR. Rickettsia amblyommatis was detected in one pool of 3 larvae and in a female of A. pacae. Additonally, we isolated Rickettsia sp. belonging to the group of spotted fevers in larvae of A. longirostre. This study reports new findings of six species of ticks and two species of Rickettsia within the SNSM.

Pulsed negative pressure myofascial vacuum therapy and percutaneous electrolysis in the treatment of lateral epicondylalgia: A single-blind randomized controlled trial.

BACKGROUND: Lateral Epicondylalgia (LE) represents one of the most common injuries of the upper limb. It is necessary to find effective treatments that reduce pain and increase functionality. PURPOSE: To determine the effects of an integrated intervention of Pulsed Negative Pressure Myofascial Vacuum Therapy (VT), Percutaneous Electrolysis (PE) and eccentric exercise (EE) in the treatment of LE compared versus Manual Therapy soft tissue mobilization (MT) and Ultrasound therapy (US) and EE. STUDY DESIGN: Single-blind randomized controlled trial. METHODS: Forty participants, with unilateral LE, were randomly divided into two groups: VT + PE + EE group (n = 20) and MT + US + EE group (n = 20). The VT + PE + EE group received one weekly session for four weeks and a regimen of EE daily at-home, and the MT + US + EE group received 10 sessions over a period of two weeks and a regimen of EE daily at-home. Numerical pain rating scale (NPRS), range of motion (ROM) pressure pain threshold (PPT) and function (PRTEE questionnaire) were measured before treatment, at the end of treatment, and at one- and three-month follow-ups. RESULTS: The statistically significant improvements were found post-treatment, favoring the VT + PE group in pain intensity (p < 0.001; ES = 0.408), PRTEE-S Pain (p = 0.001; ES = 0.377), PRTEE-S Specific function (p = 0.004; ES = 0.306) and PRTEE-S Total (p = 0.001; ES = 0.355). The VT + PE + EE treatment showed greater effectiveness than the MT + US + EE treatment at immediate post-treatment, as well as at the one-month and three-months follow-up. CONCLUSIONS: VT and PE added to an EE program could be an effective treatment for pain, ROM, PPT, and function in patients with LE.

Association of adiposity and its changes over time with COVID-19 risk in older adults with overweight/obesity and metabolic syndrome: a longitudinal evaluation in the PREDIMED-Plus cohort.

BACKGROUND: Cross-sectionally, older age and obesity are associated with increased coronavirus disease-2019 (COVID-19) risk. We assessed the longitudinal associations of baseline and changes in adiposity parameters with COVID-19 incidence in older adults at high cardiovascular risk. METHODS: This analysis included 6874 men and women (aged 55-75 years) with overweight/obesity and metabolic syndrome in the PREDIMED-Plus lifestyle intervention trial for cardiovascular risk reduction. Body weight, body-mass-index (BMI), waist circumference, waist-to-height ratio (WHtR), and a body shape index (ABSI) were measured at baseline and annual follow-up visits. COVID-19 was ascertained by an independent Event Committee until 31 December 2021. Cox regression models were fitted to evaluate the risk of COVID-19 incidence based on baseline adiposity parameters measured 5-6 years before the pandemic and their changes at the visit prior to censoring. RESULTS: At the time of censoring, 653 incident COVID-19 cases occurred. Higher baseline body weight, BMI, waist circumference, and WHtR were associated with increased COVID-19 risk. During the follow-up, every unit increase in body weight (HRadj (95%CI): 1.01 (1.00, 1.03)) and BMI (HRadj: 1.04 (1.003, 1.08)) was associated with increased COVID-19 risk. CONCLUSIONS: In older adults with overweight/obesity, clinically significant weight loss may protect against COVID-19. TRIAL REGISTRATION: This study is registered at the International Standard Randomized Controlled Trial (ISRCT; http://www.isrctn.com/ISRCTN89898870 ).

Hot Brownian Motion of Thermoresponsive Microgels in Optical Tweezers Shows Discontinuous Volume Phase Transition and Bistability.

Microgels are soft microparticles that often exhibit thermoresponsiveness and feature a transformation at a critical temperature, referred to as the volume phase transition temperature. Whether this transformation occurs as a smooth or as a discontinuous one is still a matter of debate. This question can be addressed by studying individual microgels trapped in optical tweezers. For this aim, composite particles are obtained by decorating  Poly-N-isopropylacrylamide (pNIPAM) microgels with iron oxide nanocubes. These composites become self-heating when illuminated by the infrared trapping laser, performing hot Brownian motion within the trap. Above a certain laser power, a single decorated microgel features a volume phase transition that is discontinuous, while the usual continuous sigmoidal-like dependence is recovered after averaging over different microgels. The collective sigmoidal behavior enables the application of a power-to-temperature calibration and provides the effective drag coefficient of the self-heating microgels, thus establishing these composite particles as potential micro-thermometers and micro-heaters. Moreover, the self-heating microgels also exhibit an unexpected and intriguing bistability behavior above the critical temperature, probably due to partial collapses of the microgel. These results set the stage for further studies and the development of applications based on the hot Brownian motion of soft particles.

Omics biomarkers and an approach for their practical implementation to delineate health status for personalized nutrition strategies.

Personalized nutrition (PN) has gained much attention as a tool for empowerment of consumers to promote changes in dietary behavior, optimizing health status and preventing diet related diseases. Generalized implementation of PN faces different obstacles, one of the most relevant being metabolic characterization of the individual. Although omics technologies allow for assessment the dynamics of metabolism with unprecedented detail, its translatability as affordable and simple PN protocols is still difficult due to the complexity of metabolic regulation and to different technical and economical constrains. In this work, we propose a conceptual framework that considers the dysregulation of a few overarching processes, namely Carbohydrate metabolism, lipid metabolism, inflammation, oxidative stress and microbiota-derived metabolites, as the basis of the onset of several non-communicable diseases. These processes can be assessed and characterized by specific sets of proteomic, metabolomic and genetic markers that minimize operational constrains and maximize the information obtained at the individual level. Current machine learning and data analysis methodologies allow the development of algorithms to integrate omics and genetic markers. Reduction of dimensionality of variables facilitates the implementation of omics and genetic information in digital tools. This framework is exemplified by presenting the EU-Funded project PREVENTOMICS as a use case.

Neuroinflammation in Acute Ischemic and Hemorrhagic Stroke.

PURPOSE OF REVIEW: This review aims to provide an overview of neuroinflammation in ischemic and hemorrhagic stroke, including recent findings on the mechanisms and cellular players involved in the inflammatory response to brain injury. RECENT FINDINGS: Neuroinflammation is a crucial process following acute ischemic stroke (AIS) and hemorrhagic stroke (HS). In AIS, neuroinflammation is initiated within minutes of the ischemia onset and continues for several days. In HS, neuroinflammation is initiated by blood byproducts in the subarachnoid space and/or brain parenchyma. In both cases, neuroinflammation is characterized by the activation of resident immune cells, such as microglia and astrocytes, and infiltration of peripheral immune cells, leading to the release of pro-inflammatory cytokines, chemokines, and reactive oxygen species. These inflammatory mediators contribute to blood-brain barrier disruption, neuronal damage, and cerebral edema, promoting neuronal apoptosis and impairing neuroplasticity, ultimately exacerbating the neurologic deficit. However, neuroinflammation can also have beneficial effects by clearing cellular debris and promoting tissue repair. The role of neuroinflammation in AIS and ICH is complex and multifaceted, and further research is necessary to develop effective therapies that target this process. Intracerebral hemorrhage (ICH) will be the HS subtype addressed in this review. Neuroinflammation is a significant contributor to brain tissue damage following AIS and HS. Understanding the mechanisms and cellular players involved in neuroinflammation is essential for developing effective therapies to reduce secondary injury and improve stroke outcomes. Recent findings have provided new insights into the pathophysiology of neuroinflammation, highlighting the potential for targeting specific cytokines, chemokines, and glial cells as therapeutic strategies.

Disdainful Hookups: a Powerful Social Determinant of Health.

The health consequences of gender violence, a global health and social problem, are increasingly studied. Among its roots, research has identified a coercive dominant discourse imposing the idea that masculinities and relationships marked by abuse and domination are more attractive than egalitarian ones. To prevent the health consequences of gender violence, it is necessary to understand the factors that lead many adolescents to fall into it. This study aims to identify the specific mechanisms by which the coercive dominant discourse manifests in the peer group and its consequences for adolescents. Forty-one 15- and 16-year-old female adolescents from three high schools in Barcelona participated in the study. Eight communicative discussion groups were conducted to deepen on participants' perceptions regarding how peer interactions promote the learning of attraction to violence in sexual-affective relationships. The results show that the participants perceived and experienced different types of coercion to have violent relationships in their peer group interactions. Those interactions fostered the reproduction of the association between sexual-affective attraction and males with aggressive attitudes and behaviors. Many peers coerce others to have disdainful hookups which have very negative health consequences for the victims, including suicidal ideation and committing suicide. Some peer groups become a risk developmental context for female adolescents as far as they foster the coercive dominant discourse, push some young women to engage in violent sporadic relationships, and even harass some others afterwards. This clarifies the importance of peer group-level interventions when addressing the health consequences of gender violence in adolescence.

Two-dimensional phase unwrapping based on Fourier transforms and the Yukawa potential spectrum.

The two-dimensional phase unwrapping problem (PHUP) has been solved with discrete Fourier transforms (FTs) and many other techniques traditionally. Nevertheless, a formal way of solving the continuous Poisson equation for the PHUP, with the use of continuous FT and based on distribution theory, has not been reported yet, to our knowledge. The well-known specific solution of this equation is given in general by a convolution of a continuous Laplacian estimate with a particular Green function, whose FT does not exist mathematically. However, an alternative Green function called the Yukawa potential, with a guaranteed Fourier spectrum, can be considered for solving an approximated Poisson equation, inducing a standard procedure of a FT-based unwrapping algorithm. Thus, the general steps for this approach are described in this work by considering some reconstructions with synthetic and real data.

Evaluation of the PECARN rule for traumatic brain injury applied to infants younger than 3 months and creation of a modified, age-specific rule.

Infants < 3 months with minor head trauma (MHT) are a particularly vulnerable group, though few studies have focused specifically on these patients. We aimed to evaluate the application of the PECARN prediction rule, designed for clinically important traumatic brain injury (ciTBI) in children < 2 years in infants < 3 months, and create a specific prediction rule for this population. We conducted a prospective multicenter observational study in 13 pediatric emergency departments (PEDs) in Spain. The PECARN rule was applied to all patients. A new specific prediction rule for infants < 3 months of age was created. The main outcome measures were (1) ciTBI, (2) TBI evidenced on computed tomography (CT) scan, and (3) isolated skull fracture (ISF). Telephone follow-up was conducted for all patients over the 4 weeks after the initial PED visit. Of 21,981 children with MHT, 366 (1.7%) were < 3 months old and 195 (53.3%) underwent neuroimaging, including 37 (10.1%) with CT scan. The sensitivity and negative predictive value (NPV) of the PECARN prediction rule for ciTBI were 100% (95% CI, 20.7-100) and 99.7% (95% CI, 98.4-100%), respectively. Of the 230 infants (62.8%) who met the PECARN low-risk criteria, none had ciTBI, 1 (0.4% overall, 95% CI, 0-2.4) had TBI on CT, and 2 (0.9% overall; 95% CI, 0.1-3.1) had an ISF. Among the 136 infants (37.2%) who did not meet the PECARN low-risk criteria, 1 (0.3% overall; 95% CI, 0-1.5) had ciTBI, 11 (8.1% overall; 95% CI, 4.1-14.0) had TBI on CT, and 18 (13.2% overall; 95% CI, 8-20.1) had an ISF. The sensitivity and NPV of the Spanish prediction rule for ciTBI were 100% (95% CI, 20.7-100) and 100% (95% CI, 98.4-100%), respectively. No infants in the registry developed complications during follow-up. CONCLUSION: The PECARN rule for infants < 2 years old accurately identified infants < 3 months old at low risk for ciTBI in our population, although the adapted Spanish rule presented here could be even more accurate. WHAT IS KNOWN: • Infants younger than 3 months are vulnerable to minor blunt head trauma due to their age and to difficulties in assessing the subtle symptoms and minimal physical findings detected on examination. • A low threshold for CT scan is recommended in this population. WHAT IS NEW: • PECARN rule for infants < 2 years old is an adequate tool with which to identify infants < 3 months old at low risk for clinically important traumatic brain injury. • Spanish rule could identify even more low-risk infants without overlooking important outcomes but it should be validated to confirm its predictive capacity.

EVALUATION OF THE INCLUSION OF SPECTRAL DOMAIN OPTICAL COHERENCE TOMOGRAPHY IN A TELEMEDICINE DIABETIC RETINOPATHY SCREENING PROGRAM: A Real Clinical Practice.

PURPOSE: To evaluate whether combining spectral domain optical coherence tomography with monoscopic fundus photography using a nonmydriatic camera (MFP-NMC) improves the accuracy of diabetic macular edema (DME) referrals in a teleophthalmology diabetic retinopathy screening program. METHODS: We conducted a cross-sectional study with all diabetic patients aged 18 years or older who attended screening from September 2016 to December 2017. We assessed DME according to the three MFP-NMC and the four spectral domain optical coherence tomography criteria. The sensitivity and specificity obtained for each criterion were estimated by comparing them with the ground truth of DME. RESULTS: This study included 3,918 eyes (1,925 patients; median age, 66 years; interquartile range, 58-73; females, 40.7%; once-screened, 68.1%). The prevalence of DME ranged from 1.22% to 1.83% and 1.54% to 8.77% on MFP-NMC and spectral domain optical coherence tomography, respectively. Sensitivity barely reached 50% in MFP-NMC and less for the quantitative criteria of spectral domain optical coherence tomography. When macular thickening and anatomical signs of DME were considered, sensitivity increased to 88.3% and the false DMEs and non-gradable images were reduced. CONCLUSION: Macular thickening and anatomical signs showed the highest suitability for screening, with a sensitivity of 88.3% and a specificity of 99.8%. Notably, MFP-NMC alone missed half of the true DMEs that lacked indirect signs.

Identifying critical inhalation technique errors in Dry Powder Inhaler use in patients with COPD based on the association with health status and exacerbations: findings from the multi-country cross-sectional observational PIFotal study.

BACKGROUND: Correct inhaler use depends on a complex interplay of factors, including device preparation and generating sufficient inspiratory flow. It is currently unknown which inhalation technique errors can be considered critical in Chronic Obstructive Pulmonary Disease (COPD) patients on Dry Powder Inhaler (DPI) maintenance therapy. OBJECTIVE: To investigate the association between inhalation technique errors and health status or exacerbations in patients with COPD. Additionally, the association between the number of errors and COPD outcomes was determined. METHODS: The PIFotal study is a cross-sectional multi-country observational study in a primary care setting, including 1434 COPD patients aged ≥ 40 years (50.1% female; mean age 69.2 yrs) using a DPI for their maintenance therapy. Inhalation technique was video recorded and scored by two independent researchers using inhaler-specific checklists. Health status was assessed with two questionnaires; the Clinical COPD Questionnaire (CCQ) and the COPD Assessment Test (CAT). The number of moderate and severe exacerbations in the past 12 months was recorded. Critical errors were identified based on their association with health status or exacerbations through multi-level prediction models adjusted for identified confounding. RESULTS: Errors in inhalation technique steps 'Breathe in', 'Hold breath', and 'Breathe out calmly after inhalation' were significantly associated with poorer CCQ and CAT outcomes and thus deemed critical. None of the errors were significantly associated with moderate exacerbations. Patients with errors 'Preparation', 'Hold inhaler in correct position during inhalation', and 'Breathe in' had significantly more severe exacerbations, and therefore these errors were also deemed critical. 81.3% of patients with COPD made at least one critical error. Specific combinations of errors were associated with worse outcomes. The more inhalation technique errors identified, the poorer the health status and the higher the exacerbation rate. CONCLUSION: In this study, we identified multiple critical inhalation technique errors in COPD patients using DPIs each associated with poorer outcomes. Explorative analysis revealed that specific combinations of errors may be of clinical relevance, especially those related to the inhalation manoeuvre. COPD outcomes worsened with increasing error count. These results warrant further prospective longitudinal studies to establish the effect of correcting these errors on COPD control. TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT04532853 (31/08/2020).

Semiquantitative analysis of cerebral [18F]FDG-PET uptake in pediatric patients.

BACKGROUND: Glycolytic metabolism in the brain of pediatric patients, imaged with [18F]  fluorodeoxyglucose-positron emission tomography (FDG-PET) is incompletely characterized. OBJECTIVE: The purpose of the current study was to characterize [18F]FDG-PET brain uptake in a large sample of pediatric patients with non-central nervous system diseases as an alternative to healthy subjects to evaluate changes at different pediatric ages. MATERIALS AND METHODS: Seven hundred ninety-five [18F]FDG-PET examinations from children < 18 years of age without central nervous system diseases were included. Each brain image was spatially normalized, and the standardized uptake value (SUV) was obtained. The SUV and the SUV relative to different pseudo-references were explored as a function of age. RESULTS: At all evaluated ages, the occipital lobe showed the highest [18F]FDG uptake (0.27 ± 0.04 SUV/year), while the parietal lobe and brainstem had the lowest uptake (0.17 ± 0.02 SUV/year, for both regions). An increase [18F]FDG uptake was found for all brain regions until 12 years old, while no significant uptake differences were found between ages 13 (SUV = 5.39) to 17 years old (SUV = 5.52) (P < 0.0001 for the whole brain). A sex dependence was found in the SUVmean for the whole brain during adolescence (SUV 5.04-5.25 for males, 5.68-5.74 for females, P = 0.0264). Asymmetries in [18F]FDG uptake were found in the temporal and central regions during infancy. CONCLUSIONS: Brain glycolytic metabolism of [18F]FDG, measured through the SUVmean, increased with age until early adolescence (< 13 years old), showing differences across brain regions. Age, sex, and brain region influence [18F]FDG uptake, with significant hemispheric asymmetries for temporal and central regions.

Model-Based Control of a 4-DOF Rehabilitation Parallel Robot with Online Identification of the Gravitational Term.

Parallel robots are being increasingly used as a fundamental component of lower-limb rehabilitation systems. During rehabilitation therapies, the parallel robot must interact with the patient, which raises several challenges to the control system: (1) The weight supported by the robot can vary from patient to patient, and even for the same patient, making standard model-based controllers unsuitable for those tasks since they rely on constant dynamic models and parameters. (2) The identification techniques usually consider the estimation of all dynamic parameters, bringing about challenges concerning robustness and complexity. This paper proposes the design and experimental validation of a model-based controller comprising a proportional-derivative controller with gravity compensation applied to a 4-DOF parallel robot for knee rehabilitation, where the gravitational forces are expressed in terms of relevant dynamic parameters. The identification of such parameters is possible by means of least squares methods. The proposed controller has been experimentally validated, holding the error stable following significant payload changes in terms of the weight of the patient's leg. This novel controller allows us to perform both identification and control simultaneously and is easy to tune. Moreover, its parameters have an intuitive interpretation, contrary to a conventional adaptive controller. The performance of a conventional adaptive controller and the proposed one are compared experimentally.